The overall objective of this research is the elucidation of the cellular mechanisms concerned with hormone production and secretion in the thyroid gland, and a delineation of the physiological factors involved in the regulation of these processes. In particular, since the principal regulatory agent concerned is TSH, this study is focused largely on the mechanism of action of this hormone. The experimental approach in these studies is through in vitro techniques using trypsin dispersed thyroid cells, and thyroid tissue slices or lobes. The cell preparation retains the capacity for active transport of iodide, and for the production of thyroglobulin and iodothyronine hormone moieties; moreover, it responds to TSH with an activation of each of these processes. However, since the dispersed cells are free of colloid, they cannot be used in studies of the colloid resorption and hormone secretion processes. For this purpose, thyroid tissue slices and lobes are used instead. Using these in vitro test systems, the stimulatory effects of TSH on virtually all phases of the hormone synthesis and secretion processes can be demonstrated and studied. Furthermore, the TSH also stimulates endocytosis, respiration, and the synthesis of many cellular constituents. In order to clarify the mechanisms involved in the development of so complex a pattern of effects, it is important to identify the earliest responses and to determine if these may reflect a primary action of TSH, to which the other responses may occur in consequence. At the present time, a major concern of this research program is the mode of action of cyclic AMP in initiating the endocytic response, and also the nature of the influences of cyclic AMP on other aspects of cellular function.